[Diagnosis, surveillance, and management of familial leukemia]

Recently, the modern technique of comprehensive genomic analysis has identified both somatic mutations originating from tumor cells and germline mutations as causative genes of inherited familial leukemias among which Fanconi anemia and Li-Fraumeni syndrome are well known. Pathogenic germline mutations occur in various pathways, affecting DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, neutrophil development, and other critical cellular processes. The clinical manifestations of germline mutations present a wide phenotypic spectrum of patients displaying congenital anomalies, early-onset myelodysplastic syndrome, or no medical problems until the developing leukemia. The use of genetic tests to identify these affected persons will significantly benefit cancer surveillance and subsequent therapeutic interventions. Although familial leukemia treatment usually focuses on children, it is important for clinicians to recognize that familial leukemias can occur at any age, even among older adults. Genetic counseling after diagnosis is essential, and an immediate referral to experts in each disease is recommended.